SynthesisJournal of the National Cancer Institute2021
Optimizing Survival and the Changing Landscape of Targeted Therapy for Intermediate and Advanced Hepatocellular Carcinoma: A Systematic Review.
Synthesis in Journal of the National Cancer Institute, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma.Clinical and molecular hepatology · 2022Guideline
- The association between antibiotic use and outcomes of HCC patients treated with immune checkpoint inhibitors.Frontiers in immunology · 2022Pooled it
- Hepatology: Emerging Paradigms in MASLD, Viral Hepatitis, Cholestatic Liver Disease, Portal Hypertension and Hepatocellular Carcinoma: Summary of the First Annual Paris International Liver Meeting 2026.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Inhibition of LDHA promotes GSDME-dependent pyroptosis by activating RIG-I-like receptor signaling.Apoptosis : an international journal on programmed cell death · 2026Article
- Outcome prediction model for patients with unresectable hepatocellular carcinoma treated with targeted therapy.Scientific reports · 2025Article
- Efficacy of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma: survival outcomes and prognostic factors from a systematic review and meta-analysis.Hepatobiliary surgery and nutrition · 2025Article
- Role of immune checkpoint inhibitor combinations in resectable and unresectable, embolization-eligible hepatocellular carcinoma.Therapeutic advances in medical oncology · 2025Review
- Efficacy and liver function preservation with donafenib combined with transarterial chemoembolization in unresectable hepatocellular carcinoma: An ALBI grade analysis.Frontiers in oncology · 2025Article
- The Trend of the Treatment of Advanced Hepatocellular Carcinoma: Combination of Immunotherapy and Targeted Therapy.Current treatment options in oncology · 2024Review
- Mechanisms and clinical landscape of N6-methyladenosine (m6A) RNA modification in gastrointestinal tract cancers.Molecular and cellular biochemistry · 2024Review
- Advancements in Immunotherapeutic Treatments for Hepatocellular Carcinoma: Potential of Combination Therapies.International journal of molecular sciences · 2024Review
- Immune checkpoint inhibitors in gastrointestinal malignancies: an Umbrella review.Cancer cell international · 2024Review
- Efficacy and Safety Analysis of Transarterial Chemoembolization Plus Donafenib With or Without Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma: A Prospective, Single-Arm, Single-Center, Phase II Clinical Study.Journal of hepatocellular carcinoma · 2024Article
- Synergistic Effects of Nanoscale CaOInternational journal of nanomedicine · 2024Article
- Immunotherapy for Advanced Hepatocellular Carcinoma-a Large Tertiary Center Experience.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2023Article
- Value of Non-tumoral Liver Volume in the Prognosis of Large Hepatocellular Carcinoma Patients After R0 Resection.Journal of clinical and translational hepatology · 2023Article
- Article
- Systemic Therapy for Advanced Hepatocellular Carcinoma: Current Stand and Perspectives.Cancers · 2023Review
- 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma.Journal of liver cancer · 2023Review
- Multilayered insights: a machine learning approach for personalized prognostic assessment in hepatocellular carcinoma.Frontiers in oncology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSystemic therapy for hepatocellular carcinoma (HCC) consisting of the tyrosine kinase inhibitor sorafenib has remained unchanged for over a decade, although results from phase III targeted therapy trials have recently emerged. This review considers available phase III evidence on the use and sequencing of targeted therapy for intermediate and advanced non-locoregional therapy (LRT) eligible HCC and discusses implications for clinical practice.
methodsPublished and presented literature on phase III data reporting on targeted therapy for advanced HCC that was not eligible for loco-regional therapies was identified using the key search terms "hepatocellular cancer" AND "advanced" AND "targeted therapy" AND "phase III" OR respective aliases (PRISMA).
resultsTen phase III trials assessed targeted therapy first-line and eight following sorafenib. In the first-line, atezolizumab plus bevacizumab statistically significantly improved overall survival (OS) and patient-reported outcomes (PROs) compared with sorafenib, while lenvatinib demonstrated non-inferior OS. Following progression on sorafenib, statistically significant OS improvements over placebo were seen for cabozantinib and regorafenib in unselected patients and for ramucirumab in those with baseline α-fetoprotein≥400 ng/mL. Based on improved OS and PROs, atezolizumab plus bevacizumab appears to be a preferred first-line treatment option for intermediate or advanced non-LRT eligible HCC. Phase III data informing sequencing of later lines of treatment is lacking. Therefore, sequencing principles are proposed that can be used to guide treatment selection.
conclusionsOngoing trials will continue to inform optimal therapy. Multiple targeted therapies have improved OS in intermediate or advanced non-LRT eligible HCC, although optimal sequencing is an area of ongoing investigation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.